The latest example of the corrupting influence of the pharmaceutical industry on health care policy is the composition of FDA’s advisory panel that last week endorsed the marketing of lethal COX-2 pain killers. A front page article in today’s New York Times (below) reports that 10 of the 32 panelists on FDA’s advisory committee swung the votes last week in favor of allowing the continued marketing of painkillers that induce fatal heart attacks and strokes had ties with those drugs’ manufacturers–Pfizer and Merck.

“If the 10 advisers had not cast their votes, the committee would have voted 12 to 8 that Bextra should be withdrawn and 14 to 8 that Vioxx should not return to the market. The 10 advisers with company ties voted 9 to 1 to keep Bextra on the market and 9 to 1 for Vioxx’s return.”

The 10 panelists were identified by Merril Goozner of The Center for Science in the Public Interest from disclosures in medical journals and other public documents. Other panelists may have similar conflicts that have not yet been identified.

Major, pervasive conflicts of interest among senior scientists at the National Institutes of Health were documented by the Los Angeles Times beginning with a major expose on December 7, 2003. The scope and severity of NIH scientists’ conflicts of interest is staggering – 94% of the top paid NIH scientists failed to report their financial deals with pharmaceutical companies. Several Congressional hearings were held in 2004, and a request by Congressional staff sent to just 20–out of several hundred pharmaceutical companies – yielded 100 names of NIH scientists with whom the companies had financial deals. These 100 represent the tip of an iceberg.

The scientists who receive the highest government salaries, continue to deny all and have embarked on a battle against restrictions on their supplemental income. Multiple investigations confirmed the evidence uncovered by the LA Times, leading Dr. Elias Zerhouni, director of NIH, to finally issue new conflict of interest regulations, effective Feb. 3, 2005. But as Dr. Zerhouni predicted, the hardest part is to change the culture at NIH: “It’s easy to come up with regulations. It’s not easy to change a culture.”

The new rules are meant to root out conflicts of interest and prevent major ethical abuses affecting the safety of patients and the integrity of medicine. The new rules will bring NIH staff scientists in line with federal legislation prohibiting government employees from having conflicts of interest or using insider information for self-enrichment.

But the NIH scientists are furious about a requirement that they divest themselves of pharmaceutical company stocks. Incredibly, they seem to have found support from apologists at the Washington Post.

Earlier this week, a front page article, accompanied by an editorial, supported the disgruntled NIH scientists who had used their position and insider knowledge. Scientists at NIH have a sense of entitlement to be free to strike stock option deals with companies for whom they conducted clinical trials, to engage in lucrative lecture and consultancy deals–while drawing the highest level government salaries.

The Post reported that an NIH investigation found that: “as much as 80 percent of the seeming improprieties were actually the result of errors by government investigators.” However, as has been amply demonstrated, NIH self-investigations have no credibility. The editorial said the rules “went too far.” “They threaten to harm the ability of the institutes to attract and retain top scientists…”

This is an astonishing about face, from a July 5, 2004, editorial, “Double Dipping at NIH” which raised doubts whether Dr. Zerhouni’s announcement that he would impose “drastic changes” to curtail conflicts of interest would be enough:

“Dr. Zerhouni’s prescription, which goes beyond his original recommendations, may turn out not to be strong enough medicine. It’s a legitimate question whether any outside consulting at all should be allowed.”

Ten of the 32 government drug advisers who last week endorsed continued marketing of the huge-selling pain pills Celebrex, Bextra and Vioxx have consulted in recent years for the drugs’ makers, according to disclosures in medical journals and other public records. If the 10 advisers had not cast their votes, the committee would have voted 12 to 8 that Bextra should be withdrawn and 14 to 8 that Vioxx should not return to the market. The 10 advisers with company ties voted 9 to 1 to keep Bextra on the market and 9 to 1 for Vioxx’s return. The votes of the 10 did not substantially influence the committee’s decision on Celebrex because only one committee member voted that Celebrex should be withdrawn.

Eight of the 10 members said in interviews that their past relationships with the drug companies had not influenced their votes. The two others did not respond to phone or e-mail messages. Researchers with ties to industry commonly serve on Food and Drug Administration advisory panels, but their presence has long been a contentious issue.

The agency has said it tries to balance expertise – often found among those who have conducted clinical trials of the drugs in question or otherwise studied them – with potential conflicts of interest. Several of the panel members flagged with conflicts said most or all of the money went not to themselves but to their universities or institutions.

The Center for Science in the Public Interest, an advocacy group in Washington that maintains a large database of scientists’ industry ties culled from disclosures in medical journals and other public documents, analyzed the panel members’ affiliations at the request of The New York Times. The center has been a frequent critic of the F.D.A. and of the pharmaceutical industry. The center’s analysis may understate the industry ties of the panel participants because some ties may not have been previously disclosed publicly.

Dr. Sheldon Krimsky, a science policy expert at Tufts University, said such conflicts were common on F.D.A. advisory panels. The agency often conceals these conflicts, and studies have shown that, taken as a whole, money does influence scientific judgments, Dr. Krimsky said. He added, “F.D.A. has to work harder to fill panels with people without conflicts, and if they feel they have the best committee, they at least ought to make it transparent.”

But Dan Troy, a Washington lawyer who was until last year the agency’s general counsel, said that finding knowledgeable experts without financial conflicts was difficult. Suggesting that such conflicts skew a panel’s decisions “buys into an overly conspiratorial view of the world,” Mr. Troy said.

A spokeswoman for the F.D.A. said no one at the agency would comment on specific panel members’ industry ties. Before each of three meetings of the advisory board last week, an agency secretary read a statement absolving panel members of conflicts of interest because the committee’s agenda involved “issues of broad applicability and there are no products being approved.” The secretary also said, “The Food and Drug Administration acknowledges that there may be potential conflicts of interest, but because of the general nature of the discussions before the committee, these potential conflicts are mitigated.”

But the committee took nine votes, three for each drug, on whether Celebrex, Bextra or Vioxx hurt the heart, should continue to be marketed and, if so, under what restrictions. These votes were deeply important to the three companies – Merck, Pfizer and Novartis – that came before the committee. Indeed, shares of Merck and Pfizer soared last Friday after the panel’s votes. Ten members of the panel have worked in some capacity in recent years for Merck, the maker of Vioxx; Pfizer, the maker of Celebrex and Bextra; or Novartis, which is applying to sell Prexige, a very similar pill discussed by the panel, according to the public disclosures. An 11th panel member, Dr. Jack Cush, a rheumatologist at Presbyterian Hospital in Dallas, said a disclosure that he once consulted for Pfizer was incorrect, so he was excluded from the analysis.

Of the 30 votes cast by the 10 panel members on whether Celebrex, Bextra and Vioxx should continue to be marketed, 28 favored the drugs. Among the 66 votes cast by the remaining 22 members of the panel, just 37 favored the drugs.

Dr. Steven Abramson, a rheumatologist at New York University School of Medicine who was on the panel, has consulted for Pfizer and Novartis. “The F.D.A. is looking for people who understand the science behind these medicines,” and such an understanding often results from working with drug makers, he said.

Dr. John Farrar, a neurologist at the University of Pennsylvania who has received research support from Pfizer and is a panel member, agreed. “I think F.D.A. would have a hard time finding people who are good at what they do who never spoke to a pharmaceutical company,” he said.

But Dr. Curt Furberg, a panel member and an epidemiologist at Wake Forest University who had no ties to any of the drug companies, said he was “uncomfortable with the Pfizer-friendly undertone” at the meeting. And he worried that Pfizer’s financial relationships with some panel members might have played a role in setting that tone.

Joan Wainwright, a spokeswoman for Merck, said the company had had no role in choosing any of the scientists on the panel. Merck has made no decision on whether it will reintroduce Vioxx, Ms. Wainwright said. “We look forward to discussing the outcomes of the meeting with the F.D.A. and other regulatory authorities,” she said.

Andy McCormick, a spokesman for Pfizer, said the company had no plans to withdraw Bextra from the market. He also said that Pfizer had played no role in helping to choose the panel. Critics of the drug industry said they were not surprised that the panel’s decisions would have been different if scientists with financial ties to the companies had recused themselves from the votes.

“My employees usually vote for me as well,” said W. Mark Lanier, a lawyer in Houston who represents people who have sued Merck after taking Vioxx and suffering heart attacks or strokes.

Some lawyers and Wall Street analysts said last week that the panel’s decision would help to protect Merck and Pfizer from lawsuits. But juries will be more skeptical of the decision after they learn about the composition of the panel, Mr. Lanier said.

Christopher A. Seeger, a lawyer in New York with many Vioxx clients, said the fact that scientists had not recused themselves simply highlighted the close ties between the drug industry and academic researchers. He said researchers were afraid to say anything negative about new drugs because doing so might jeopardize their chances of participating in clinical trials and publishing papers.

Several panel members said the important split on the committee was not so much between those with industry ties and those who did not have those ties but between experts who treat arthritis patients and those who do not. Dr. Cush was angry that the voices of the panel’s rheumatologists were nearly drowned out by statisticians and others who do not have to cope with anguished patients every day.

Dr. Furberg said clinicians often wanted access to therapies without understanding the devastating public health consequences of their prescribing decisions. Celebrex, Bextra and Vioxx have never been proved in clinical trials to cure pain any better than ibuprofen or more than a dozen other, older pain pills. “Fifty patients a day probably die from those drugs, and who is speaking for them?” Dr. Furberg said.

Dr. Alastair Wood, an associate dean at Vanderbilt University and the panel’s chairman, said he was disappointed that the F.D.A. failed to disclose the financial conflicts of the panel’s participants before each day’s meeting. “I’m a great believer in letting it all hang out,” he said. Still, Dr. Wood said that even with its conflicts the panel was a tough critic of the drugs. Many of the panel members who were among the narrow majorities approving continued marketing of Bextra and Vioxx did so only with the stipulation that severe restrictions be imposed on their uses, he noted. He said he expected that the uses of the drugs would be confined to very limited patient populations.

Most of the 100 or so National Institutes of Health researchers who the agency has said are under investigation for allegedly engaging in secret deals with pharmaceutical and biotechnology companies have been cleared by NIH investigators, according to agency officials.

The unexpected finding that as much as 80 percent of the seeming improprieties were actually the result of errors by government investigators has undermined the rationale behind NIH Director Elias A. Zerhouni’s recent decision to impose severe restrictions on the personal activities and finances of all of the agency’s more than 5,000 employees, said scientists and NIH officials upset about the new rules.

Scientists said the finding is fueling an already simmering backlash among them and others on the Bethesda campus who feel that the new restrictions will seriously damage the crown jewel of the nation’s biomedical research enterprise.

Zerhouni has repeatedly said that a congressional committee’s discovery several months ago that about 100 NIH scientists had failed to notify the agency about their outside deals, as required, compelled him to impose the new limits. The rules, which took effect Feb. 3, are forcing thousands of employees and their family members to sell stock holdings. They also ban scientists from accepting even uncompensated professorships and board positions with professional societies on their own time.

The finding that most of the allegations are false has many scientists complaining that Zerhouni did not get a better measure of the problem before succumbing to pressure from Congress and the government ethics office to prohibit virtually every kind of outside collaboration and to demand across-the-board divestitures.

Some are organizing to fight the changes through internal lobbying and legal challenges.

“All of us are in favor of strong regulations to avoid conflicts of interest,” said Abner L. Notkins, chief of experimental medicine at the National Institute of Dental and Craniofacial Research. But the new rules, he said, “go to an extreme. We’re hearing from a number of people that they want to leave. And a number of people who were about to start here have said they are now thinking they will not come.”

NIH Deputy Director Raynard S. Kington, who serves as chief ethics officer for the $28 billion agency, defended the decision to institute major restrictions despite the fact that as few as 20 scientists out of the agency’s thousands of employees may have violated approval and disclosure rules.

“The number is just one dimension of this problem,” he said. “There is also the severity of the problems.”

One scientist allegedly collected hundreds of thousands of dollars in fees and travel reimbursements over five years as a result of largely undisclosed activities.

Kington would not say how many scientists have been found to have violated disclosure rules, but he noted that the new rules were the result of multiple reviews.

“We came to the conclusion the system was not at a point where we could carefully monitor and manage the types of conflict we can identify,” Kington said. He added that the agency is considering creating some exceptions to the new rules.

The confusion over the alleged failure to report consulting arrangements dates back to last year, when congressional investigators asked 20 pharmaceutical and biotechnology companies for the names of all NIH scientists with whom they had consulting arrangements. When Congress compared those lists to a similar list provided by NIH officials, about 130 arrangements on the company lists involving about 100 scientists did not appear on the NIH list, suggesting that those scientists had not reported the arrangements to their NIH superiors as required.

Zerhouni, who until then had been a staunch defender of such collaborations as an important means of speeding the translation of research into marketable treatments, recently said he felt “shot in the back” when he learned that so many scientists were ignoring the rules. Convinced that “the system was broken,” he and Kington instituted the Feb. 3 restrictions.

But a detailed NIH review of the 100 or so scientists identified by the congressional inquiry has found that “more than half,” and perhaps up to 80 percent, were mistakenly implicated, said Suzanne Servis, director of the NIH Office of Management Assessment, who has been overseeing the internal review.

In some cases, discrepancies arose because NIH provided data on collaborations only through Dec. 31, 2003, while the drug companies included the names of people going into 2004 who, it turned out, had gained NIH permission.

In other cases, people whom the drug companies named as having collaborations with them had the same names as scientists at NIH but were not NIH employees.

In other cases, scientists did not appear on the NIH list because the agency had coded those scientists’ activities as something other than consultancies — the only category requested by Congress.

Neal Young, chief of hematology at the National Heart, Lung and Blood Institute, was one of those mistakenly implicated. It started with a surprise announcement last summer that he was under investigation, Young said. Over a period of weeks, he was asked to turn over more and more records, and only recently, after eight months of questions, did he receive a draft notification that he had been cleared.

At issue was a talk he gave at a company, which had been approved and properly reported in 2004.

The investigation, he said, was a “very intrusive, time-consuming and anxiety-provoking experience.” And although he has come through relatively unharmed, he is concerned about the cumulative effect of such errors on the agency’s image.

“This is really a wonderful place and one of the best deals the American public has ever gotten, and I hate to see it portrayed as badly as it’s been portrayed, and I’d hate to see it destroyed.”

A number of NIH employees are gearing up for a fight. Some have been consulting with the American Civil Liberties Union, which is considering the argument that the broad restrictions infringe on employees’ rights to privacy and free speech.

Another group on the Bethesda campus, known as the Assembly of Scientists, is pursuing other legal strategies to keep the rules from affecting the vast majority of employees who have no power over NIH purse strings. Some noted that the rules affect not only well-paid scientists and administrators but also low-level secretaries and clerks who could stand to lose significant sums if forced to divest stock holdings.

Already, the new rules have begun to discourage medical residents and fellows who are being recruited to the agency’s newly expanded clinical center — the nation’s largest medical research hospital, which taxpayers just financed to the tune of $1 billion and which opened in October.

Hundreds of the nation’s foremost physician-researchers rotate through the center for two- or three-year stints to run studies and care for patients undergoing experimental therapies. But with the new rules insisting that even these temporary employees and their family members must sell their biomedical stock portfolios and forgo various professional privileges, some top candidates are now reconsidering options at other institutions where such restrictions do not apply, according to administrators tracking the recruitment process.

“There are a lot of things that can be done at NIH that can’t be done anywhere else in the field of clinical research, but you can’t run the clinical programs without the interns,” said Elaine Jaffe, chief of hematopathology at the National Cancer Institute, who knows of at least two top candidates having second thoughts. “Having just spent a lot of money on a new hospital, I’d hardly think you’d want to shut it down.”

Scientists with long histories at NIH are as frustrated as incoming interns. One scientist who, under the new rules, was informed he could not accept an unpaid adjunct professorship at Johns Hopkins University was told he might be unduly influenced in favor of the university because the appointment came with free campus parking — even though the scientist, who has no say over grant decisions, said he was happy to refuse the parking pass.

“I think this is the end of the [on-campus] research program if people are not allowed to do these professional activities, which are all unreimbursed,” said Alan Neil Schechter, chief of molecular biology and genetics at the National Institute of Diabetes and Digestive and Kidney Diseases.

Kington said he is aware that the rules could hurt recruiting and is hopeful that the agency could make exceptions for temporary or short-term employees.

Post navigation

Donate to AHRP

To make a tax-deductible contribution, you may use Paypal:

Or mail your check, payable to AHRP:

Alliance for Human Research Protection (AHRP)142 West End Ave., Suite 28P
New York, NY 10023

Random Quote

The bitter truth was that AIDS did not just happen to America – It was allowed to happen by an array of institutions, all of which failed to perform their appropriate tasks to safeguard the public health … There was no excuse, in this country and in this time, for the spread of a deadly new epidemic.